Respiratory Distress Syndrome (RDS) is the major cause of morbidity and mortality in premature infants. The primary etiology ofthe RDS is developmental immaturity of surfactant production. However, there is significant heterogeneity in pulmonary outcomes among infants of the same gestational age who have similar clinical risk factors. Studies suggest a significant genetic contribution to the risk of RDS. The specific aims ofthe proposal are 1) to examine if common genetic variations (single nucleotide polymorphisms) in the genes that code for Surfactant Proteins A, B, and C and ATP binding cassette transporter 3 are associated with RDS, and 2) to evaluate if severity of RDS is associated with these genetic variations. To accomplish these aims, we will employ a unique setting, the Northern California Kaiser Permanente Medical Care Program, which has a large defined population (>35;000 births/year), integrated information systems, and readily available critical information including an electronic medical record, radiology results, and laboratory test results. Using a nested case control design, we will obtain DNA samples from infants with RDS (n~160) and controls matched by gestational age, gender, and ethnicity. Conditional multivariate logistic regression techniques will be used to evaluate for associations between these genetic variants and RDS. In the infants with RDS, we will use multivariate linear regression techniques to compare measures of RDS seventy (duration of supplemental oxygen use and duration of assisted ventilation) between infants who have genetic variants and those who do not, controlling for confounders such as gestational age. My long-term career goal is to become a genetic epidemiologist, focusing on genetic determinants of neonatal diseases. During the K23 award period I plan to enhance my understanding of basic genetics, develop hands-on experience with the tools used in genetic analysis (DNA extraction, genotyping, etc.), familiarize myself with advanced biostatistical techniques that can be applied to genomic studies, and comprehensd how to use electronic databases to identify subjects, phenotype individuals, and obtain additional risk factor information. PUBLIC HEALTH RELEVANCE: Common variations in an infant's genetic code may explain why some infants develop RDS or have more severe disease. This variation may not be important unless the infant is born prematurely or has other risk factors. Knowing if an infant has any of these common variations may allow physicians to customize prevention and treatment strategies, based upon this genetic information.